The Autoimmunity Center of Excellence at the Albert Einstein College of Medicine will encompass research projects, an infrastructure for clinical trials and an administrative core. This Center reflects an interdisciplinary approach to autoimmune disease. It involves a collaboration of clinicians and basic scientists that is focused on translational studies to develop new therapeutic strategies. The research component will be directed by Betty Diamond and includes three research projects. Each project has the goal of developing new targets for therapy in autoimmune disease. The first project (PI: Anne Davidson) is a study of the effects of statins alone or in conjunction with CTLA-4Ig in the NZB/W mouse model of lupus. This project will include a study of the effect of statins on peripheral blood mononuclear cells of lupus patients. The second project (PI: Betty Diamond) is a study of the effect of CD22 over-expression on B cell development and on autoantibody production in murine models of SLE and includes a study of a CD22 polymorphism reported to associate with lupus. Overall it will explore whether inhibition of CD22 represents a useful therapeutic strategy. The third project (PI: Stanley Nathenson) is a biophysical study of the polymorphism of murine two microglobulin that is required for the expression of diabetes in NOD mice. This study will provide a comprehensive biophysical characterization of the features of TCR/MHC-peptide complexes that are directly relevant to eliciting diabetes. These studies promise to provide the atomic and molecular mechanisms responsible for disease development and thus may lead to novel strategies for the design of therapeutics that will limit disease-associated T cell reactivity. A clinical infrastructure is described (Clinical Director: Cynthia Aranow) that is capable of performing clinical trials in autoimmune rheumatic diseases, type 1 diabetes, autoimmune hematologic diseases, and inflammatory bowel disease. In addition, there are proposals for a clinical trial of DNase I in serologically active, clinically inactive lupus and for a trial of statin therapy as a steroid sparing agent in rheumatoid arthritis. Finally, the Center will include an administrative core for coordination and implementation of Center activities.